The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans
Abstract
Modifications of the interactions between endoplasmic reticulum (ER) and mitochondria, defined as mitochondria-associated membranes (MAMs), were recently shown to be involved in the control of hepatic insulin action and glucose homeostasis, but with conflicting results. Whereas skeletal muscle is the primary site of insulin-mediated glucose uptake and the main target for alterations in insulin-resistant states, the relevance of MAM integrity in muscle insulin resistance is unknown. Deciphering the importance of MAMs on muscle insulin signaling could help to clarify this controversy. Here, we show in skeletal muscle of different mice models of obesity and type 2 diabetes (T2D) a marked disruption of ER-mitochondria interactions as an early event preceding mitochondrial dysfunction and insulin resistance. Furthermore, in human myotubes, palmitate-induced insulin resistance is associated with a reduction of structural and functional ER-mitochondria interactions. Importantly, experimental increase of ER-mitochondria contacts in human myotubes prevents palmitate-induced alterations of insulin signaling and action, whereas disruption of MAM integrity alters the action of the hormone. Lastly, we found an association between altered insulin signaling and ER-mitochondria interactions in human myotubes from obese subjects with or without T2D compared with healthy lean subjects. Collectively, our data reveal a new role of MAM integrity in insulin action of skeletal muscle and highlight MAM disruption as an essential subcellular alteration associated with muscle insulin resistance in mice and humans. Therefore, reduced ER-mitochondria coupling could be a common alteration of several insulin-sensitive tissues playing a key role in altered glucose homeostasis in the context of obesity and T2D.
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In the citing paper
“Particularly, the dysregulation of the interactions between mitochondria and the ER has been reported to be implicated in the pathogenesis of insulin resistance (Flamment et al., 2012; Sebastian et al., 2012; Tubbs et al., 2018).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“Remarkably, the interaction between mitochondria and the sarcoplasmic reticulum (SR) has been confirmed in skeletal muscle (Tubbs et al., 2018; Thoudam et al., 2019).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“Not surprisingly, also in consideration of the pivotal role of skeletal muscle in the regulation of glucose homeostasis, the dysregulation of MAMs may contribute to skeletal muscle insulin resistance in mice and humans (Tubbs et al., 2018; Thoudam et al., 2019).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“Mitochondria-SR interactions have been reported to be reduced in the skeletal muscle of high-fat or genetically induced obese and diabetic mice as well as in human primary myotubes treated with palmitic acid (Tubbs et al., 2018)”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
In the citing paper
“indicating that the MAM reduction may represent a link between mitochondrial dysfunction and insulin resistance in skeletal muscle.”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Tubbs et al., 2018
Citations
Cites
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Endoplasmic reticulum-mitochondria contacts: Function of the junction
Rowland, A. A., & Voeltz, G. K. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3440 · Cited by 1,018 · cited 1×
“Indeed, mitochondria and ER interact at contact points, called mitochondria-associated ER membranes (MAMs), to exchange calcium (Ca) and lipids, thus regulating cell metabolism and fate (4,5).”
BackgroundRegulation of mitochondrial ATP synthesis by calcium: Evidence for a long-term metabolic priming
Jouaville, L. S., Pinton, P., Bastianutto, C., Rutter, G. A., & Rizzuto, R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.24.13807 · Cited by 831
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Self-citationArruda, A. P., Pers, B. M., Parlakgül, G., Güney, E., Inouye, K., & Hotamışlıgil, G. S. (2014) · Nature Medicine · doi:10.1038/nm.3735 · Cited by 741
Sebastián, D., Hernández-Alvarez, M. I., Segalés, J., Sorianello, E., Muñoz, J. P., Sala, D., Waget, A., Liesa, M., Paz, J. C., Gopalacharyulu, P., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108220109 · Cited by 673
The role of mitochondria in the pathogenesis of type 2 diabetes
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The coming of age of the mitochondria–ER contact: a matter of thickness
Giacomello, M., & Pellegrini, L. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.52 · Cited by 471
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1 of the 46 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Sheperd, Citrate synthase from rat liver, 11
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Items 201–202 of 202
Mitochondria–Endoplasmic Reticulum Crosstalk in Pancreatic β-Cell Stress: A Driver of Diabetes
Niinuma, S. A., Takemoto, A. S.-N., Khalil, W. J., Butler, A. E., & Moin, A. S. M. (2026) · Cells · doi:10.3390/cells15191733
Tri-Organelle Contact Sites Integrate Metabolic Function in Health and Disease
Mukunda, S. G., Khan, M. M., Marshall, A., Hinton, A., & Katti, P. (2026) · Contact · doi:10.1177/25152564261496636
Metadata
- Authors
- Tubbs, E., Chanon, S., Robert, M., Bendridi, N., Bidaux, G., Chauvin, M.-A., Ji-Cao, J., Durand, C., Gauvrit-Ramette, D., Vidal, H., Lefai, E., & Rieusset, J.
- Affiliations
- Lyon 1 Université (FR)
- Laboratoire de Recherche en Cardiovasculaire, Métabolisme, Diabétologie et Nutrition (CarMeN), INSERM U1060, INRA U1397, Institut National des Sciences Appliquées-Lyon, Université Claude Bernard Lyon1, Oullins, Lyon, France
- Corresponding author
- Rieusset, Jennifer
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2018-01-11
- Volume
- 67
- Issue
- 4
- Pages
- 636-650
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2783880365
- Cited by
- 202
- References
- 46
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 26 · 2023: 19 · 2022: 22 · 2021: 35 · 2020: 32 · 2019: 23 · 2018: 9
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- INSERM
- Agence Nationale de la Recherche (ANR-09-JCJC-0116)
- Fondation pour la Recherche Médicale (DRM20101220461)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- mitochondria-associated endoplasmic reticulum membranes, ER-mitochondria communication, muscle insulin resistance, skeletal muscle, type 2 diabetes, obesity, palmitate, insulin signaling, mitochondrial dysfunction, glucose homeostasis, myotubes
- MeSH terms
- Aged, Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Endoplasmic Reticulum, Female, Glucose, Homeostasis, Humans, Insulin, Insulin Resistance, Intracellular Membranes, Male, Middle Aged, Mitochondria, Muscle, Obesity, Palmitates, Signal Transduction, Muscle, Skeletal, Muscle Fibers, Skeletal, Mice
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